Molecular mechanisms of Caenorhabditis elegans - Bacillus interactions

Abstract

Pathogens represent strong evolutionary forces driving the complexity of the host defense system. The nematode Caenorhabditis elegans has been widely used as a genetically amenable invertebrate for studying host-pathogen interactions. While the C. elegans model provided invaluable insights into innate defense pathways against infections, it remains to be discovered what the role of these pathways is in other nematodes and how they shape the evolution of bacterial pathogenicity. The nematode Pristionchus pacificus has been extensively used for comparative studies with C. elegans, linking developmental biology, ecology and population genetics. In this context, drastic ecological and morphological differences between two nematodes served as a starting point for studying bacterial interactions and immune response of the two nematodes in a comparative manner. Aiming to find suitable pathogens for these comparative studies, I isolated and tested 768 natural Bacillus strains for the pathogenicity to nematodes. This resulted in the isolation of the fastest known C. elegans killer B. thuringiensis DB27, which P. pacificus is completely resistant to. Using system wide analysis, we showed that C. elegans and P. pacificus respond to B. thuringiensis DB27 or any other given pathogen in strikingly different ways, regulating a very different set of effector genes. Using the C. elegans - B. thuringiensis DB27 model, I (i) elucidated C. elegans defense mechanisms against the pathogen, revealing a novel role for Dicer in antibacterial immunity; (ii) with the help of whole genome sequencing, discovered that two novel Cry21 protoxins produced by B. thuringiensis DB27 act synergistically as the main nematicidal virulence factors; (iii) discovered that C. elegans commensal bacterium B. subtilis protects the worm from infection via bacteriocin-mediated pathogen inhibition. Taken together, these results not only tackle both sides of C. elegans - B. thuringiensis DB27 host-pathogen interactions, but also reveal previously unrecognized mechanism of nematode protection by commensal-mediated inhibition of the pathogen.